This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As the AIDS pandemic continues to fuel rates of tuberculosis (TB) worldwide, it is important to understand how the human immune system responds to TB in both HIV-positive and HIV-negative settings. This is critical for designing vaccines that protect against TB disease. Intact adaptive immune responses mediated by CD4+ and CD8+ T cells are essential for controlling infection with Mycobacterium tuberculosis (Mtb) but their effector functions, development into memory cells and regulation are poorly characterized. We are characterizing the progression of TB-specific immune responses and their regulation within an individual undergoing antibiotic treatment. We are studying the regulation of Mtb antigen-specific immune responses in HIV negative and HIV positive individuals before and during standard tuberculosis antibiotic therapy. Patient enrollment for these studies is ongoing at Grady Hospital in close partnership between basic science (Rengarajan) and clinical (Ray) investigators. Since detailed immunological studies that longitudinally follow TB and HIV-TB co-infected patients do not exist, this project will lay the foundation for future studies in larger patient populations, specifically in settings where AIDS and TB are co-endemic.